Drugs Acting On Peripheral Nervous System
Drugs Acting On Peripheral Nervous System
Drugs Acting On Peripheral Nervous System
Nervous System
P-2
Blood pressure
Heart rate
Respiration
Body Temperature
Glandular Secretion
Digestion
Reproduction
Acetylcholine
Norepinephrine
Epinephrine
Site of release
All preganglionic
neurons of ANS; all
postganglionic neurons
of parasympathetic
system; Some
sympathetic
postganglionic neurons
to sweat glands
Most sympathetic
postganglionic
neurons; adrenal
medulla (20% of
secretion)
Adrenal medulla
(80 % of
secretion)
Receptor
1, 2, 1 (adrenergic)
1, 2, 1, 2
(adrenergic)
Enzymatic degradation
by cholinesterase
Metabolic
transformation by
catechol-Omethyltransferase within
liver
Termination of
activity
1. Mesentery
2. Outer longitudinal
muscle layer
3. Myenteric plexus
4. Peritoneum
and Serosa
6. Inner circular
muscle layer
5. Submucosa
7. Submucosal plexus
8. Mucosa
Subserosal plexus
P-3
Diarrhea / Vomiting / Intestinal colic
Constipation / Gastroparesis / Paralytic ileus
GERD (Could be due to a lax lower
esophageal sphincter)
Cholinergic and anti-cholinergic drugs
Opioid receptors inhibit acetylcholine
release
Antiemetic drugs
Central Autonomic
input
P-4
Periaqueductal
gray matter
Parabrachial
nucleus
Cortex
Dorsal motor vagal
nucleus
Amygdala
Hypothalamus
Nucleus Ambiguus
Ventrolateral medulla
Heart
Nucleus of the
solitary tract
Central Autonomic
Output
Periaqueductal
gray matter
Parabrachial
nucleus
Cortex
Dorsal motor vagal
nucleus
Amygdala
Hypothalamus
Nucleus Ambiguus
Parasympathetic
input
Nucleus of the
solitary tract
Ventrolateral
medulla
Sympathetic input
Heart
Intermediolateral cell column
P-6
Sympathetic System
Parasympathetic System
Limited divergence
Neuromuscular
Blocking Drugs
Action
Potential
Arrives
ACh
Ca++
ACh
ACh
Potentiate
Transmission
Pyridostigmine
Neostigmine
Distigmine
edrophonium
Synaptic
Cleft
ACh
ACh
ACh
ACh
Vesamicol
ACh
ACh
Hemicholinium
Botulinum toxin
Aminoglycosides
2+ ions
Acetate Mg
ion2+,+CaCholine
ACh
ACh
ACh
ACh
Competitive
Tubocurarine
Gallamine
Pancuronium
Vecuronium
Atracurium
Rocuronium
Depolarizing
Suxamethonium
Na+
Acetylcholinesterase
inhhbitors
G
P
C
R
Post-Synaptic
membrane
III
All preganglionic
nerves secrete Ach.
Ganglionic blocking
drugs block
transmission.
(e.g.Mecamylamine)
Ciliary
III
VII
VII
Pterygopalatine
VII
Submandibular
IX
IX
Otic
T1
T1
T2
T3
Sympathetic
Pre-ganglionic
Blue
Post-ganglionic
Pink
X Vagus
T2
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
S3
S3
S4
Nervi erigentes
S4
Parasympathetic
Pre-ganglionic
Red
Post-ganglionic
Green
Sympathetic
Sympathetic
Parasympathetic
Parasympathetic
P-23
Sympathetic
Lacrimal gland
Xerostomia:
Pilocarpine
III
VII
IX
Sympathetic
Pre-ganglionic
Blue
Post-ganglionic
Pink
T1
T1
T2
T2
T3
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
S3
S3
S4
S4
Parasympathetic
Pre-ganglionic
Red
Post-ganglionic
Green
Superior (jugular)
ganglion of Vagus
nerve
Inferior (nodose)
ganglion of Vagus
nerve
Vagus nerve
Lacrimal gland
III
VII
IX
Sympathetic
Pre-ganglionic
Blue
Post-ganglionic
Pink
T1
T1
T2
T2
T3
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
S3
S3
S4
S4
Parasympathetic
Pre-ganglionic
Red
Post-ganglionic
Green
Asthma / COPD:
Ipratropium
Beta blockers. NO
Pilocarpine. NO
Bronchoconstriction
Parasympathetic
Left vagus
Sympathetic trunk,
middle cervical
ganglion
Sympathetic
trunk, thoracic
ganglia
Thoracic aortic
plexus
Vagus nerve on
aortic arch
Cardiac
plexus
Lacrimal gland
III
VII
IX
Sympathetic
Pre-ganglionic
Blue
Post-ganglionic
Pink
T1
T1
T2
T2
T3
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
S3
S3
S4
S4
Parasympathetic
Pre-ganglionic
Red
Post-ganglionic
Green
Anhydrosis:
Neoplasms
Spinal cord
injuries
Lumbar
sympathectomy
Lacrimal gland
III
VII
IX
Sympathetic
Pre-ganglionic
Blue
Post-ganglionic
Pink
T1
T1
T2
T2
T3
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
S3
S3
S4
S4
Parasympathetic
Pre-ganglionic
Red
Post-ganglionic
Green
Lacrimal gland
Pheochromacytoma:
Alpha blockers
Beta blockers ?
III
VII
IX
Sympathetic
Pre-ganglionic
Blue
Post-ganglionic
Pink
T1
T1
T2
T2
T3
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
S3
S3
S4
S4
Parasympathetic
Pre-ganglionic
Red
Post-ganglionic
Green
Lacrimal gland
Glycogenolysis /
gluconeogenesis:
2 effects.
Beta blockers may
mask the effects of
anti-diabetic therapy
III
VII
IX
Sympathetic
Pre-ganglionic
Blue
Post-ganglionic
Pink
T1
T1
T2
T2
T3
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
S3
S3
S4
S4
Parasympathetic
Pre-ganglionic
Red
Post-ganglionic
Green
Lacrimal gland
III
VII
IX
Sympathetic
Pre-ganglionic
Blue
Post-ganglionic
Pink
T1
T1
T2
T2
T3
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
S3
S3
S4
S4
Parasympathetic
Pre-ganglionic
Red
Post-ganglionic
Green
P
A
R
A
S
Y
M
P
A
T
H
E
T
I
C
S
Y
M
P
A
T
H
E
T
I
C
Lacrimal gland
Overflow
incontinence
Urge incontinence
Antimuscarinics
III
VII
IX
Sympathetic
Pre-ganglionic
Blue
Post-ganglionic
Pink
T1
T1
T2
T2
T3
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
S3
S3
S4
S4
Parasympathetic
Pre-ganglionic
Red
Post-ganglionic
Green
Parasympathetic
Premature
Labor:
2 receptors
cause
relaxation of
both pregnant
and non
pregnant uteri.
Beta agonists
e.g. ritodrine
Sympathetic
Pre-ganglionic
Blue
Post-ganglionic
Pink
Lacrimal gland
III
VII
IX
T1
T1
T2
T2
T3
T3
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
T4
T5
T6
T7
T8
T9
T10
T11
T12
L1
L2
L3
L4
L5
S1
S2
S3
S3
S4
S4
Parasympathetic
Pre-ganglionic
Red
Post-ganglionic
Green
+++++++++++++++++++++++++
Cell
Receptor down-regulation
Cell
Receptor up-regulation
P-24
Muscle Relaxant
A muscle relaxant is a drug which affects
skeletal muscle function and decreases the
muscle tone.
Neuromuscular blockers and spasmolytics are
often grouped together as muscle relaxants
Muscle Relaxants
Muscle Relaxants
How skeletal muscle relaxation can be
achieved?
High doses of volatile anesthetics
Regional anesthesia
Administration of neuromuscular blocking agents
Muscle Relaxants
Muscle relaxants must not be given without
adequate dosage of analgesic and hypnotic
drugs
Inappropriately given : a patient is paralyzed
but not anesthetized
Muscle Relaxants
Nerve stimulation
Release of Acetylcholine (Ach)
Postsynaptic events
Muscle Relaxants
Depolarizing muscle relaxant
Succinylcholine
Cardiovascular
Fasciculation
Muscle pain
Increase intraocular pressure
Increase intragastric pressure
Increase intracranial pressure
Hyperkalemia
Malignant hyperthermia
Intermediate acting
Atracurium
Short acting
Mivacurium
Alteration of responses
Temperature
Acid-base balance
Electrolyte abnormality
Age
Concurrent diseases
Drug interactions
Alteration of responses
Concurrent diseases
Neurologic diseases
Muscular diseases
Myasthenia gravis
Myasthenic syndrome (Eaton-Lambert synrome)
Liver diseases
Kidney diseases
Alteration of responses
Drug interactions
Inhalation agents
Intravenous anesthetics
Local anesthetics
Neuromuscular locking drugs
Antibiotics
Anticonvulsants
Magnesium
Antagonism of Neuromuscular
Blockade
Effectiveness of anticholinesterases depends on the
degree of recovery present when they are
administered
Anticholinesterases
Neostigmine
Onset 3-5 minutes, elimination half life 77 minutes
Dose 0.04-0.07 mg/kg
Antagonism of Neuromuscular
Blockade
What is the mechanism of action?
Inhibiting activity of acetylcholineesterase
More Ach available at NMJ, compete for sites on
nicotinic cholinergic receptors
Action at muscarinic cholinergic receptor
Bradycardia
Hypersecretion
Increased intestinal tone
Antagonism of Neuromuscular
Blockade
Muscarinic side effects are minimized by
anticholinergic agents
Atropine
Dose 0.01-0.02 mg/kg
Scopolamine
glycopyrrolate
Reversal of Neuromuscular
Blockade
Goal : re-establishment of spontaneous
respiration and the ability to protect
airway from aspiration
Local Anesthetics
All local anesthetics in current use are derivatives
or analogues of cocaine, a drug extracted from
coca leave
Mode of action
Na+ channels exist in three states resting, open
and inactivated.
The inactivated state occurs after the open state
when the membrane is repolarising and this
discourages premature activation until the next
action potential arrives.
Local anaesthetics bind most strongly to Na+
channels in the inactivated state thus contributing to
the blocking effect.
Acute toxicity
Main concern is CNS and cardiac toxicity
CNS
Tinnitus, dizziness, lightheadedness are early signs
Anxiety disorientation loss of consciousness
seizures respiratory arrest
Cardiac
Hypotension
All local anesthetics are negative inotropes
PVC wide QRS Multiform vtach vfib, or
Pattern with bupivacaine
Bradycardia asystole
Pattern with bupivacaine + lidocaine
Acute Toxicity
With most drugs, CNS toxicity proceeds cardiac
toxicity, providing a warning of impending disaster.
Key response: maintain oxygenation and normal CO2!
Acute toxicity
Risk of seizure and/or cardiovascular collapse
is increased by:
Cold temperature (slows metabolism)
Metabolic or respiratory acidosis
Hypoxia
Treatment of overdose
Airway:
100% oxygen
Intubate if necessary to ventilate
CNS:
Break seizure with propofol, thiopental, or midazolam
Cardiovascular
Amiodarone has demonstrated efficacy. Use 300 mg
Lidocaine would be a particularly poor choice!
Resuscitation difficult with bupivacaine, more frequently
successful in animal studies following ropivacaine and
levobupivacaine overdose.
Allergies
Amides
True allergies to amide
anesthetics are
EXCEEDINGLY rare
Esters
Uncommon
Allergic reactions
probably
related
PABA.
Common ingredient
sun-screen.
are
to
in
Allergies
Allergies to local anesthetics are commonly reported
by patients.
True allergies to local anesthetics of either class are
rare.
Most allergic responses that have been carefully
evaluated are:
Psychogenic
Reactions to preservatives (e.g., metabisulfite) or latex
cardiovascular response to epinephrine.
Methemoglobinemia
10%: clinical anoxia
60%: stupor, coma, and death.
Documented with benzocaine, prilocaine
may
exacerbate
Drug Interactions
Esters
are
pseudocholinesterase
metabolized
by